Arthritis is an inflammatory disease of arthroses. Main examples of arthritis are rheumatoid arthritis and its analogous diseases wherein inflammation is observed in arthroses.
In particular, rheumatoid arthritis, also referred to as chronic rheumatism, is polyarthritis chronica whose main lesion is inflammatory changes in synovial membranes of internal layers of articular capsules. Arthritis such as rheumatoid arthritis is progressive and causes articular disorders such as articular deformation, tetany, etc. When an effective treatment is not carried out and the disease worsens, serious physical disorders are often caused.
Hitherto, in treatment of such arthritis, chemotherapy has been carried out using steroids such as adrenal cortical hormones (e.g., cortisone, etc.), etc.; non-steroidal anti-inflammatory agents such as aspirin, piroxicam, indomethacin, etc.; gold preparations such as gold thiomalate, etc.; antirheumatic agents such as chloroquine preparations, D-penicillamine, etc.; antipodagrics such as colchicine, etc.; immunosuppressive agents such as cyclophosphamide, azathioprine, methotrexate, levamisole, etc.
However, these drugs have problems such as serious side effects, side effects making their long-term use difficult, insufficient efficacy, inefficacy against arthritis which has already produced the symptoms.
Therefore, in clinical treatment of arthritis, drugs having low toxicity and excellent effects in the prophylaxis and treatment of arthritis have been required.
Various quinoline derivatives having an acyl group, hydroxyalkyl group or amidated carboxyl group at the 3-position have been synthesized. For example, Journal of Heterocyclic Chemistry, Vol. 12, p. 737 (1975) discloses 4-phenylquinoline derivatives having a hydroxymethyl group or amidated carboxyl group at the 3-position. The Journal of Organic Chemistry, Vol. 31, p. 3852 (1966) and Nippon Kagaku Zasshi, Vol. 90, p. 81 (1969) disclose 4-phenylquinoline derivatives having an acetyl group at the 3-position. Further, Chemical Abstracts, Vol. 79, 42371h (1973) discloses anti-inflammatory activity of 3-acylquinoline derivatives. The substituents at the 2-position of the compounds disclosed in these literature are, however, limited to an alkyl group, phenyl group, etc.